Macrophage migration inhibitory factor in the mouse hippocampus promotes neuroinflammation and cognitive dysfunction following anesthesia and surgery.

Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia and surgery, particularly in elderly individuals. Although progress has been made in understanding its causes, the modulatory mechanism of neuroinflammation in POCD is still not fully understood. Macrophage migration inhibitory factor (MIF) has been demonstrated to be crucial in neuroinflammation and neuronal damage, but its role in POCD remains unclear. This study aimed to explore the role of MIF in neuroinflammation and cognitive impairment following anesthesia and surgery. We revealed that there is a notable cognitive deficit in mice following anesthesia and surgery, accompanied by exacerbated neuroinflammation. Which was marked by elevated levels of pro-inflammatory cytokines and the activation of microglia and astrocytes in mice hippocampus. Notably, there was a pronounced upregulation of MIF expression in the serum and hippocampus, particularly within neurons and microglia, following anesthesia and surgery. MIF deficiency improved cognitive impairment and inhibited neuroinflammation, as well as decreasing release of pro-inflammatory cytokines, reducing activation of microglia and astrocytes, and performing the preservation of dendritic spine structure and neuronal integrity. This finding implies that MIF plays a crucial role in mediating neuroinflammation and cognitive dysfunction following anesthesia and surgery, and targeting MIF-mediated neuroinflammation may offer a novel strategy to POCD.